Thiazole → 2,2-Difluoro-1-(1,3-thiazol-2-YL)ethan-1-one

This procedure is based on literature, see: Krasovskiy, A.; Krasovskaya, V.; Knochel, P. Angew. Chem. Int. Ed. 2006, 45, 2958. Thiazole (5.7 mL, 80 mmol) in THF (100 mL) was added to a stirred, cooled (0° C.) solution of isopropylmagnesium chloride-lithium chloride (1.18 M in THF, 74.9 mL, 88 mmol) in THF (75 mL) then the mixture was stirred at room temperature for 1 hour. Then the solution was cooled to −20° C. and ethyl difluoroacetate (9.29 ml, 88 mmol) was added. The mixture was stirred for 10 minutes at −20° C., then 10 minutes at room temperature. The mixture was diluted with ethyl acetate (200 mL), washed with aqueous ammonium chloride (saturated, 200 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chromatography on silica gel, 0-90% ethyl acetate in hexanes) to give 2,2-difluoro-1-(1,3-thiazol-2-yl)ethanone (12 g, 73.6 mmol, 92% yield) as a yellow oil. MS ESI: [M+H]+ m/z 164.0.

1. temperatureThen the solution was cooled to −20° C.
2. stirringThe mixture was stirred for 10 minutes at −20° C.
3. custom10 minutes
4. customat room temperature
5. washwashed with aqueous ammonium chloride (saturated, 200 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customthe solvent was evaporated under reduced pressure
9. customThe residue was purified by column chromatography on silica gel (chromatography on silica gel, 0-90% ethyl acetate in hexanes)

ORD-Eintrag

ord-76be4dc01972446b826c0c7d2e35bafc

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08759366B2